ER alpha determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

doi:10.1016/j.omtn.2021.07.022

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24066

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24066

Title:	ER alpha determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions
Authors:	He, YH;Yeh, MH;Chen, HF;Wang, TS;Wong, RH;Wei, YL;Huynh, TK;Hu, DW;Cheng, FJ;Chen, JY;Hu, SW;Huang, CC;Chen, Y;Yu, JX;Cheng, WC;Shen, PC;Liu, LC;Huang, CH;Chang, YJ;Huang, WC
Date:	2021
Issue Date:	2022-08-05T09:47:18Z (UTC)
Publisher:	CELL PRESS
ISSN:	2162-2531
Abstract:	Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ER alpha) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 (DDB2) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.
URI:	http://dx.doi.org/10.1016/j.omtn.2021.07.022 https://www.webofscience.com/wos/woscc/full-record/WOS:000697094900008 https://ir.csmu.edu.tw:8080/handle/310902500/24066
Relation:	MOLECULAR THERAPY-NUCLEIC ACIDS ,2021,v25 , P536-553
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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